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Trial registered on ANZCTR


Registration number
ACTRN12615001094561
Ethics application status
Approved
Date submitted
6/10/2015
Date registered
19/10/2015
Date last updated
23/01/2019
Date data sharing statement initially provided
23/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The combination treatment of laser bypass (chorioretinal venous anastomosis) and Lucentis for the treatment of macula oedema (swelling at the back of the eye) that has occurred as a result of a central retinal vein occlusion, compared to the published results of Lucentis treatment only.
Scientific title
The combination treatment of laser induced chorioretinal venous anastomosis and Lucentis for macula oedema that is secondary to central retinal vein occlusion, compared to the published results of Lucentis treatment only, a phase IV study.
Secondary ID [1] 287582 0
Nil
Universal Trial Number (UTN)
U1111-1175-0486
Trial acronym
L-CVBS Extension Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Maucula oedema secondary to central retinal vein occlusion. 296379 0
Condition category
Condition code
Eye 296651 296651 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study participants will receive a combination treatment of laser bypass (chorioretinal venous anastomosis, L-CRA) and intraocular injections of Lucentis. Both treatments are approved for this condition. This is a phaseIV study that follows on from the L-CVBS study (ACTRN12612000004864). The laser L-CRA treatment will occur first, with the Lucentis injections commencing 4-5 weeks later.

The Ellex Integre S laser will be used to create the anastomosis. Two sites will be chosen, one above and one below the optic disc. Both will be over a tributary of a major quadratic vein at least 2 disc diameters away from the optic disc. It is not possible to be specific about the location as this will depend on the individual anatomical arrangement in each participant's eye. The spot size is 50um whilst the power will be up to 4W (depends on the degree of cataract), and duration of 0.1 seconds. There is only one laser treatment session that consists of two attempts to establish a functional L-CRA.

Following the L-CRA treatment, participants will commence monthly injections of Lucentis (Ranibizumab). Lucentis is a TGA approved treatment for this condition, and has recently been placed on the PBS. The Lucentis will be obtained through the PBS authority by the investigator. The dose for each intravitreal injection is 2.3mg/0.23mL(10mg/mL) solution, the volume injected is 50ul. There will be a loading dose of three injections, each at 4 week intervals. Participants will be monitored monthly until Month 6. and if during this time the participant's visual acuity drops and/or the oedema has returns, Lucentis treatment will continue (at monthly intervals) until the visual acuity and/or oedema stabilises. From Month 6- Month 12, the visits will occur once every 2 months, provided the participant's visual acuity is stable and there is no macula oedema. If an injection occurs, then the visits revert back to monthly until visual acuity and macula oedema stabilise. Likewise, in the second year of the study, visits may occur once every 3 months if visual acuity and macula oedema are stable, but if there is a drop in visual acuity and/or macula oedema returns, monthly Lucentis injections will resume until visual acuity and/or the oedema stablises. Visits may then gradually move to once very 2 months and then once every three months. In summary, participants receive 3 Lucentis injections at monthly intervals (loading dose) and then further Lucentis treatment will only be administered if visual acuity drops and/or macula oedema returns. The study duration is 2 years.



Intervention code [1] 292982 0
Treatment: Drugs
Intervention code [2] 292983 0
Treatment: Devices
Comparator / control treatment
There is no control group for this study.
The number of injections required by the participants in this study after the loading dose of Lucentis will be compared to the published results where the only treatment is Lucentis.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 296262 0
Compare the number of injections required in the combination treatment of laser bypass (L-CRA) and Lucentis in this study to published studies using monotherapy Lucentis (CRUISE, HORIZON and RETAIN studies).
Timepoint [1] 296262 0
Month 24 after the L-CRA treatment.
Secondary outcome [1] 318009 0
Mean average best visual acuity (BCVA) from baseline to months 6, 12 and 24 between the combination treatment group and previously reported data using Lucentis treatment alone.
Timepoint [1] 318009 0
Baseline, Month 6, Month 12 and Month 24 after the L-CRA treatment.
Secondary outcome [2] 318010 0
A comparison of the residual central macula thickness changes as measured by Spectral Domain OCT from baseline to month 6, 12 and 24 in the combination treatment to previously reported data using Lucentis monotherapy.
Timepoint [2] 318010 0
Baseline, Month 6, Month 12 and Month 24 after the L-CRA treatment.
Secondary outcome [3] 318018 0
Monitor retinal and choroidal vasculature remodeling with Fluorescein angiography (FA) and Indocyanine green (ICG) angiography performed at Baseline, Month 12 and Month 24.
Timepoint [3] 318018 0
Baseline, Month 12 and Month 24 after the L-CRA treatment.
Secondary outcome [4] 318019 0
Monitor the nature and sequence of changes to radial peripapillary capillaries and the deep capillary networks using optical coherence tomography angiography (OCTA) at Baseline, Month 3, Month 6, Month 12 and Month 24.
Timepoint [4] 318019 0
Baseline, Month 3, Month 6, Month 12 and Month 24 after the L-CRA treatment.

Eligibility
Key inclusion criteria
1. Foveal centre involved perfused macular oedema secondary to CRVO.
2. Mean central foveal thickness greater or equal to 250 microns on spectral domain OCT.
3. Adults greater or equal to 18 years.
4. Clear ocular media and adequate pupilaary dilation.
5. IOP less or equal to 25mmHg.
6. Written informed consent.
7. No other significant pathology.
8. Willing, committed and able to return for all clinic visits and complete all study related procedures.
9. Patients who have had a previous CRVO that has spontaneously resolved will be enrolled provided there is no evidence of macular damage that would confuse visual acuity improvements.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Brisk afferent pupillary defect.
2. Evidence on examination of any diabetic retinopathy.
3. CVA or MI within 3 months prior to Baseline.
4. Women of childbearing potential not using the contraception method(s) specified in this study, as well as women who are breastfeeding.
5. Known sensitivity to study drug(s) or class of study drug(s).
6. Use of any other investigational agent in the last 30 days.
7. Any other ocular condition in the study eye that would prevent improvement in visual acuity. e.g. macular ischaemia, underlying macular degeneration, epi-retinal membrane.
8. Neovascularisation of the iris, disc or retina.
9. Aphakia or presence of anterior chamber lens in the study eye.
10. Significant media opacities such as cataract.
11. Previous pars plana vitrectomy.
12. History of retinal detachment or surgery for retinal detachment.
13. Any condition which would preclude a patient's ability to comply with the study requirements or to be available for the duration of the study.
14. Any active infection involving ocular adnexa including infectious conjunctivitis, keratitis, sclertitis, endophthalmitis as well as idiopathic or autoimmune associated uveitis in either eye.
15. Extra capsular extraction of cataract with phacoemulsification within three months preceding baseline, or a history of post-operative complications within the last 12 months preceding baseline in the study eye (uveitis, cyclitis etc.).
16. Contra indication to pupil dilation in either eye.
17. Anticoagulation with warfarin or other significant anticoagulation drugs.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All participants will receive the combination treatment of L-CRA (laser bypass) and Lucentis injections.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
100 patients will be recruited from the Investigator's clinic at Lions Eye Institute. All participants who present with a central retinal vein occlusion who meet the study inclusion/exclusion criteria will be asked if they wish to participate in the study. Because this is a phase IV study, no sample size calculations were used to determine this number. The number is based on the experience from the previous phase III study (L-CVBS study).

Data will be continuously analysed and response patterns compared with published results using monotherapy. Individual characteristics within the data set (e.g. duration, presenting BCVA, degree of ischaemia, concurrent medical conditions, smoking etc.) will be analysed for any evidence of modification of treatment effect.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 4420 0
Lions Eye Institute Day Surgery Centre - Nedlands
Recruitment postcode(s) [1] 10633 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 292157 0
Other
Name [1] 292157 0
Lions Eye Institute
Address [1] 292157 0
Lions Eye Institute
2 Verdun St
Nedlands
Western Australia
6009
Country [1] 292157 0
Australia
Primary sponsor type
Other
Name
Lions Eye Institute
Address
Lions Eye Institute
2 Verdun St
Nedlands
6009
Western Australia
Country
Australia
Secondary sponsor category [1] 290832 0
None
Name [1] 290832 0
Address [1] 290832 0
Country [1] 290832 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293633 0
Sir Charles Gairdner Hospital Human Research Ethics Committee
Ethics committee address [1] 293633 0
Sir Charles Gairdner Hospital Human Research Ethics Committee, 2nd Floor, A Block, Sir Charles Gairdner Hospital, Hospital Ave, Nedlands, 6009, Westerm Australia.
Ethics committee country [1] 293633 0
Australia
Date submitted for ethics approval [1] 293633 0
27/10/2015
Approval date [1] 293633 0
11/12/2015
Ethics approval number [1] 293633 0

Summary
Brief summary
This is a monitoring study (phase IV) for participants with swelling in the back of the eye (macula oedema) that has been caused by a blockage to the main vein (retinal vein) draining the back of the eye (central retinal vein occlusion). The current treatment for this condition is a series of injections at monthly intervals of anti-VEGF antibodies (e.g. Lucentis or Avastin) into the back of the eye. Whilst this treatment works well, there is often an ongoing need for the eye injections. A laser treatment developed at the Lions Eye Institute, creates a channel from the retina (back of the eye) to the choroid (layer above the retina) for the blood to drain (laser bypass treatment). In the L-CVBS study participants who received the eye injections and laser bypass treatment require fewer eye injections longer term than participants who only receive the eye injections. Because the laser bypass and injection treatments work differently to address the swelling caused by the blockage, the combination of using both treatments tends to give patients a better visual outcome with fewer injections required. Recruitment for the L-CVBS study has closed, and this new study is a follow on study, where all participants will receive eye injections and the laser bypass treatment.

Participants with a macula oedema that is caused by a central retinal vein occlusion will be asked if they would like to participate in this study (consent obtained first). If eligible, all participants will receive the laser bypass treatment followed by the Lucentis injections. The standard loading dose of a monthly Lucentis injection for the first three months will be followed. Participants will be monitored monthly until Month 6. If there is evidence of macula oedema and/or vision loss, further monthly injections will be given until the participants condition stabilises. If after Month 6 visual and macula oedema stability is achieved, the visits can be extended to once every two months until Month 12. If stability is maintained from Month 12, then the visits can be extended to once every three months in the second year. But if visual acuity drops and/or if macular oedema is present, then the eye injections will resume and the visits will be monthly until stability is achieved. We hope to show that fewer injections are required to achieve visual and anatomic stability compared to studies where only Lucentis injections are used.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 60734 0
Prof Ian McAllister
Address 60734 0
Lions Eye Institute
2 Verdun St
Nedlands
6009
Western Australia
Country 60734 0
Australia
Phone 60734 0
+61 8 9381 0870
Fax 60734 0
+61 8 9381 0766
Email 60734 0
IanMcAllister@lei.org.au
Contact person for public queries
Name 60735 0
Dr Lynne Smithies
Address 60735 0
Lions Eye Institute
2 Verdun St
Nedlands
6009
Western Australia
Country 60735 0
Australia
Phone 60735 0
+61 8 9381 0790
Fax 60735 0
+61 8 9381 0766
Email 60735 0
LynneSmithies@lei.org.au
Contact person for scientific queries
Name 60736 0
Prof Ian McAllister
Address 60736 0
Lions Eye Institute
2 Verdun St
Nedlands
6009
Western Australia
Country 60736 0
Australia
Phone 60736 0
+61 8 9381 0870
Fax 60736 0
+61 8 9381 0766
Email 60736 0
IanMcAllister@lei.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
All participant data is de-identified and not linked to the participant.
Ethics approval did not include the release of individual participant data.
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
Summary results
No Results